Elucidation of the mechanisms of action by which drugs of abuse modify brain function requires knowledge of fundamental neuroscience with respect to how individual molecular components control neurotransmission and behavior. This program for predoctoral and postdoctoral fellows will provide research training in relevant neuroscience for understanding how drugs of abuse modify brain function. This interdisciplinary training program by the excellent faculty of the Graduate Program in Neurosciences at the Univ. of Calif., San Diego (UCSD) will span protein chemistry for synthesis of opioid receptor ligands, biochemistry and macromolecular structure of protein components involved in neurotransmission, and pharmacology of receptor-mediated signal neuronal systems in pain and behavior that are related to the actions of drugs of abuse. The integration of analyzing brain function at several levels-protein biochemistry as sites of drug interactions, molecular biology, neurobiology, physiology, and neuronal circuits in pain and behavior- is required for drug abuse research to elucidate how these chemical drugs modify regulatory receptors, enzymes, and other components that regulate neurotransmission and behavior. This training program will instruct six predoctoral students and two postdoctoral trainees in multidisciplinary and integrated research areas in neuroscience for the goal of enhancing our knowledge of how drugs of abuse modify brain function. Each trainee will be mentored by a primary NIDA-funded faculty advisor of this training program. Incorporation of modern and interdisciplinary approaches will be achieved with a secondary faculty mentor with expertise in current neuroscience disciplines that will enhance drug abuse research. Multidisciplinary research projects involving the training faculty will be developed. Exchange of scientific knowledge among trainees and faculty will be achieved through coursework, seminars, formal scientific presentations and scientific discussions. The high quality faculty, and their commitment to research training, will allow this program to train young scientists who will possess the appropriate expertise and scientific knowledge for elucidation of drug actions. Furthermore, modern up-to date facilities at UCSD will be accessible to trainees, including newly established Proteomic Laboratory, bioinformatic analyses of the Protein Data Bank and protein structure at the San Diego Supercomputer Center (SDSC) that includes drug informatics, the core transgenic mouse facility, peptide synthesis and sequencing core, and molecular and cell biology facilities. Trainees of this program will acquire the knowledge required for their continued investigations on the principles of drug action to investigate mechanisms of drugs of abuse.